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Activating phosphorylation of the CDKs that control the cell cycle is a conserved step carried out by divergent enzymes in different species. Remarkably, the fission yeast Schizosaccharomyces pombe contains two CAKs -- one homologous to Cdk7 of higher eukaryotes and one superficially similar to budding yeast Cak1.

The packaging of eukaryotic nuclear DNA into chromatin poses special challenges to the Pol II transcriptional machinery, which must recognize and interact productively with DNA sequneces embedded within--and sometimes occluded by--a higher-order structure consisting of a regular array of nucleosomes. The "opening up" of chromatin to access by the transcriptional machinery is likely to be a critical and highly regulated step in gene expression, which may be perturbed in cancer cells.

The major CAK in mammalian cells is CDK7, a cyclin-dependent kinase that forms dimeric complexes with cyclin H, as well as trimeric complexes with cyclin H and the RING-finger protein, MAT1. In addition to these "free CAK" species, a fraction of CDK7 is associated (together with cyclin H and MAT1) with the general transcription factor, TFIIH.